Rhabdomyolysis: Etiology, Pathophysiology, Clinical Features, Diagnosis, and Management

Review Article

Abstract

Rhabdomyolysis is a potentially life-threatening condition characterized by the breakdown of skeletal muscle fibers and the release of intracellular components, including myoglobin, creatine kinase, potassium, and phosphate, into the circulation. Its clinical spectrum ranges from mild biochemical abnormalities to severe complications such as acute kidney injury, electrolyte disturbances, disseminated intravascular coagulation, and cardiac arrhythmias. Early recognition and treatment are essential for improving outcomes. The causes of rhabdomyolysis are diverse and can be broadly classified as traumatic, exertional, toxic, metabolic, infectious, and genetic. Traumatic causes include crush injuries, burns, and prolonged immobilization. Exertional rhabdomyolysis is increasingly reported in athletes and military personnel following intense physical activity, especially in the setting of dehydration or heat stress. Drugs and toxins, such as statins, alcohol, and illicit substances, may produce direct muscle toxicity. Metabolic and electrolyte disorders, infections, and inherited metabolic myopathies can also impair muscle cell stability and energy metabolism, leading to muscle injury. At the cellular level, damage to the muscle membrane results in increased intracellular calcium, activation of proteolytic enzymes, and muscle necrosis, with subsequent release of myoglobin and creatine kinase. Myoglobin contributes to acute kidney injury through tubular obstruction and direct nephrotoxicity, particularly in the presence of hypovolemia. Clinical manifestations are often nonspecific, and the classic triad of muscle pain, weakness, and dark urine is uncommon. Diagnosis relies mainly on markedly elevated creatine kinase levels and myoglobinuria. Treatment is primarily supportive, with early aggressive intravenous fluid administration to prevent renal complications. Prognosis depends on injury severity and prompt management.